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BREAST CANCER
Anterpreet Neki, MD , MS
MORTALITY RATES OF CANCER IN
WOMEN - 2008
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
2
IMPACT OF RESEARCH ON BREAST CANCER SCREENING
AND RISK-REDUCTION
Estimated reduction in US overall breast cancer mortality is 28-65%
(Breast cancer mortality RR >50 y- 0.78 and 40-49 y- 0.85)
• The identification of DCIS has increased 7-fold since 1980
Berry et al NEJM 2005
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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WHY HOPE ?
Stage
Distribution (%)
5-year
Relative Survival (%)
Localized (confined to primary site)
60
98.4
Regional (spread to regional lymphnodes)
33
83.9
Distant (cancer has metastasized)
5
23.8
Unknown (unstaged)
2
50.7
Stage at Diagnosis
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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Breast Cancer Is a Significant Public
Health Concern for Women – Cancer Deaths
26%
15%
9%
6%
5%
4%
40,170
Deaths
192,370
New BC Cases
3%
3%
2%
269,800 Cancer Deaths
(all sites)
2%
25%
Adapted from American Cancer Society. Cancer Facts and
Lung and bronchus
Breast
Colon and rectum
Pancreas
Ovary
Non-Hodgkin
lymphoma
Leukemia
Uterine corpus
Liver & intrahepatic
bile duct
Brain & other
nervous system
All other sites
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research2009.
Institute
Figures
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BREAST CANCER EPIDEMIOLOGY
-Most common cancer in women in the world
-commoner in developed nations (obesity,inactivity)
-14% of cancer deaths (second after lung CA)
-mortality decreased by 34% in last 2 decades
-black women have a lower rate of Breast CA, but relatively
higher mortality
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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RISK FACTORS
-1:8
-Exogenous hormones,obesity,exercise,alcohol,diet,breast density
-Older age, female
-Earlier menarche, late menopause,late first birth,nulliparity
-Benign breast disease
-Family history (5-10%): 1 deg relative,BRCA1/2 mutations,p53
-Ashkenezi jews
-Radiation exposure
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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SCREENING
-Mammographic screening : 23% reduction in breast CA
relted mortality in F 50-70 yrs, and 15% decrease in
mortality in 40-50 yrs
-Annual mammograms and MRI in BRCA mutants
starting at age 25
-Core biopsy of suspicious tissue for pathology, ER, PR,
HER2
-H/o mantle radiation: annual mammogram and MRI
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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Breast Cancer: Then and Now
Then
Now
 ~75% of women survived ≥5
years
 ~90% of women survive ≥5
years
 Mastectomy was the only
surgical option
 Lumpectomy is available
 Single-agent chemotherapy
was standard of care
 Hormonal therapy with
tamoxifen was under
investigation only
 Genes involved in breast
cancer development have not
yet been identified
 Combination chemotherapy is
the standard of care
 Hormonal therapy is widely
used
 Receptor-based therapy is
widely used
 Understanding of genetic
components have expanded
The Ohio State University Comprehensive Cancer Center –
National Cancer Institute. Available at: http://www.cancer.gov/cancertopics/cancer-advances-in-focus/breast.
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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DIAGNOSIS
Ultrasound guided core needle biopsy
ER/PR/HER2
PROGNOSIS
Size, multiple, histology, grade, lymph nodes,
proliferative rate, ER/PR, Her2,Intrinsic molecular
subtypes (luminalA/B, basal/triple negative)
OncotypeDx (node-,ER+)= Recurrance score
(low= do not benefit from chemo in addition to
hormonal therapy)
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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STAGING
T tumors size
T0-4
N Number/nature of nodes N0-3
M Metastasis
M0-1
Stage 1-4
TNM
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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TREATMENT
LOCAL
Surgery : Mastectomy
Lumpectomy+Radiation
Radiation
Hormonal therapy
Her2based (Herceptin, Pertuzumab),
Chemotherapy (>0.5 cm, LN+)
(doxorubicin,cyclophosphamide,taxol,etc)
METASTATIC
Palliative chemo, radiation, bone support
(Zometa,Xgeva)
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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BREAST CONSERVING SURGERY
Modified Radical
Mastectomy
Radical Mastectomy
Lumpectomy
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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Tam
Tam + Chemo
0.4
0.3
Intergroup Trial
For Randomization
0.2
Benefit from chemo
0.1
Distant Recurrence at 10 Years
ONCOTYPE Dx ASSAY
0.0
0
10
20
30
40
50
Recurrence
Score
Recurrence
Score
Minimal, if any, Chemo Benefit
Clear Chemo Benefit
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
Sparano, TBCI San
Antonio, 2005
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Paik S et al. NEJM 2004
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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OLD PARADIGM:
“pre-genomic era”
 Breast cancer is divided into ER+, ER Chemotherapy:
 NIH consensus conference Nov 2000:
 “It is accepted practice to offer cytotoxic chemotherapy
to most women … primary breast cancers larger than 1
cm (both node negative and positive, ER positive or
negative)”
 Hormone Therapy:
 For ER +
HER 2 neu status
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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Most Important Paradigm Shift:
Breast Cancer is not one disease
“A”
ER+
65-75%
ER-
Breast
Breast Cancer
Cancer
HER2+
15-20%
ER +
Basaloid
15%
STAGE
“B”
“Triple Negative”
BRCA 1
P53
SIZE
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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HORMONE THERAPY
Aromatase
inhibitors
SERMs
Tamoxifen
Fulvestrant
Steroidal
Non-steroidal
Exemestane
Anastrazole
Letrozole
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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ENDOCRINE RESISTANCE
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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ONCOTYPE DX ASSAY
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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Survival Improvement in Metastatic Breast
Cancer Patients
Survival, %
100
Period 1987-1993
Period 1994-2000
Censored events
75
P<0.001
50
25
0
0
12
24
36
48
60
Months
 Survival of breast cancer patients presenting with metastases at
diagnosis has improved over time, strongly suggesting that
improvement is related to treatment
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
Andre F, et al. J Clin Oncol. 2004; 22(16):3302-3308.
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SURVELLENCE
-H&P 3m for 3 yr, then 6m for 4,5 yr, then annually
-report new lumps,pain, SOB,bone pain, headaches
-genetic counselling (h/o ovarian CA, 1deg relative with
Br CA<50,>/=2 first deg or sec deg
relatives,bilateral,male relative with Br CA
-monthly self-exam
-annual mammogram
-pelvic exam if vaginal bleeding on Tamoxifen
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
28
SUMMARY
-Early diagnosis /mammogram , improved survival
-lumpectomy+radiation results in breast conservation
-prognostic new tests (OncoType Dx)call help select
cases for chemotherapy
-Improved oral Hormonal agents +/-Herceptin in patients
with appropriate receptors , help consolidate treatment
and imrove survival
-multiple new chemo/targeted /hormonal therapy
combinations to slow metastatic disease
-bone support agents available
-continued close followup ,annual mammograms
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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Stefanie Spielman Comprehensive Breast Center
OSU
— from prevention and screening through
detection, diagnosis, treatment and survivorship —
in one world-class facility.
PATIENT NAVIGATORS
Shawna Deems 614-366-1586
Naomi Harding 614-293-7020
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove
Research Institute
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